Tuning crystallization and stability of the metastable polymorph of dl-methionine by a structurally similar additive

Crystal engineering is aimed at controlling the crystal forms and desired properties from the view of molecular engineering, which is important for the production of high-value-added products. dl-Methionine (dl-met) usually crystallizes in a concomitant mixture with the known metastable alpha-form and stable beta-form from a pure aqueous solution. In this contribution, we first applied molecular dynamics (MD) simulations to study the effects of the tailor-made additive and found that dl-leucine (dl-leu) might enable us to stabilize the metastable form. To validate our idea, we performed experiments including cooling crystallization with isothermal and non-isothermal methods, nucleation induction time measurements, solvent-mediated phase transformation and crystal growth rate measurements. It was found that on increasing the concentration of dl-leu, the nucleation of the beta-form and the transformation of the alpha-form were hindered. When the concentration of dl-leu reached above 0.02 mol L-1, hexagonal crystals other than foliaceous crystals could be obtained. Hence, the metastable alpha-form of dl-met with fine crystal habits and high temporal stability was prepared.